An anti-picornaviral strategy based on the crystal structure of foot-and-mouth disease virus 2C protein

文献类型： 外文期刊

第一作者： Zhang, Chu

作者： Zhang, Chu;Qin, Bo;Gao, Xiaopan;Cui, Sheng;Zhang, Chu;Qin, Bo;Gao, Xiaopan;Cui, Sheng;Yang, Fan;Zhang, Wei;Zheng, Min;Cao, Weijun;Zheng, Haixue;Wojdyla, Justyna Aleksandra;Wang, Meitian

作者机构：

期刊名称：CELL REPORTS （ 影响因子：9.995； 五年影响因子：10.99 ）

ISSN： 2211-1247

年卷期： 2022 年 40 卷 1 期

页码：

收录情况： SCI

摘要： The foot-and-mouth disease virus (FMDV) 2C protein shares conserved motifs with enterovirus 2Cs despite low sequence identity. Here, we determine the crystal structure of an FMDV 2C fragment to 1.83 A?? resolution, which comprises an ATPase domain, a region equivalent to the enterovirus 2C zinc-finger (ZFER), and a C-terminal domain harboring a loop (PBL) that occupies a hydrophobic cleft (Pocket) in an adjacent 2C mole-cule. Mutations at ZFER, PBL, and Pocket affect FMDV 2C ATPase activity and are lethal to FMDV infectious clones. Because the PBL-Pocket interaction between FMDV 2C molecules is essential for its functions, we design an anti-FMDV peptide derived from PBL (PBL-peptide). PBL-peptide inhibits FMDV 2C ATPase activ-ity, binds FMDV 2C with nanomolar affinity, and disrupts FMDV 2C oligomerization. FMDV 2C targets lipid droplets (LDs) and induces LD clustering in cells, and PBL-peptide disrupts FMDV 2C-induced LD clustering. Finally, we demonstrate that PBL-peptide exhibits anti-FMDV activity in cells.

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